Adjuvant Lenvatinib for High-Risk CNLC IIb/IIIa Hepatocellular Carcinoma After Curative Hepatectomy: A Prospective Exploratory Study

Abstract

Objective: The risk of hepatocellular carcinoma (HCC) recurrence following surgical resection remains high, approaching 50%-70% at 5 years, with the highest risk occurring in the first year after resection. This study aimed to evaluate the efficacy and safety of lenvatinib as adjuvant therapy for HCC. Methods: In this open-label, single-arm, prospective, multicenter Phase II clinical study, a total of 51 hCC patients with China Liver Cancer (CNLC) stage IIb/IIIa (ie tumor number ≥ 4 or vascular invasion, equivalent to BCLC B/C) who underwent R0 resection 4–6 weeks after curative surgery were enrolled. Patients received lenvatinib for up to 12 months, at a dose of 8 mg/day for body weight < 60 kg, or 12 mg/day for ≥ 60 kg. Patients were followed up every 2 months for a median of 24.1 months. Results: The median recurrence-free survival (RFS) was 16.1 months, with a 12-month RFS rate of 60.4%, exceeding the historical rate of under 50% in similar high-risk populations. The 12-month overall survival (OS) rate was 93.6%, while median OS was not reached. Treatment-related adverse events (TRAEs) occurred in 88.0% of patients, with ≥ grade 3 TRAEs in 14.0%, including thrombocytopenia and proteinuria in 6.0% of patients each, and leukopenia, neutropenia, elevated aspartate aminotransferase, and elevated alanine aminotransferase in 2.0% of patients each. AEs leading to the interruption of lenvatinib occurred in 6.0% of patients, and dose reduction was required in 18% of patients. No deaths were observed. Conclusion: Lenvatinib may be an effective adjuvant therapy for patients with CNLC stage IIb/IIIa HCC after R0 hepatectomy. However, the findings are limited by the single-arm design and small patient cohort, necessitating larger randomized controlled trials for validation.